Parkinson's disease is the second most prevalent neurodegenerative disease. There are over 4 million patients in the world and the incidence rate is rapidly increasing with a rising elderly population. The symptoms of Parkinson's disease typically show progressive locomotive defects such as rigidity, tremor, bradykinesia of the limbs, and postural instability, and non-locomotive defects such as cognitive dysfunction, depression, sleep disorder, and pain.
In the aspect of anatomy, selective degeneration of dopaminergic neurons in the substantia nigra is the pathological hallmark of Parkinson's disease. When 60-80% of dopaminergic neurons in the substantia nigra are decreased, extrapyramidal tracts cannot efficiently work and the symptoms of Parkinson's disease occur.
Parkinson's disease is currently treated using dopamine replacement therapies. Because of the loss of dopamine-containing neurons in the brain, oral levodopa and dopamine agonist drugs are mainstay therapies for Parkinson's disease. These drugs are generally administered several times a day or more to increase dopamine levels in the brain. One oral formulation that is administered three to four times a day is the combination of levodopa and carbidopa.
However, the blood levels resulting from oral administration may often fluctuate between high blood concentrations (e.g., peaks) that are often associated with side effects such as dyskinesias (e.g., diminished voluntary movements and the presence of involuntary movements) and low blood levels (e.g., troughs) that are often associated with return of the motor symptoms (“off” time) of Parkinson's disease. As the disease progresses and oral drug therapy is continued, the peak-trough effects may become more exaggerated and severe leading to poor patient compliance.
To counter the peak-trough effects of short acting oral formulations, sustained release oral formulations are currently available to treat Parkinson's disease. Sustained release oral ropinirole is an example of one such formulation, which is marketed by GlaxoSmithKline under the name Requip XL®. This sustained release formulation is administered less frequently than the oral immediate release formulation and generally contributes to better patient compliance.
However, Parkinson's disease patients often have dysfunctional gastric motility, especially as the disease progresses, which can lead to delayed emptying of the stomach and delayed absorption of the oral formulation and thus a delayed onset of dopaminergic symptom relief.
It would therefore be desirable to provide injectable ropinirole compositions and methods that do not rely on a functioning gastrointestinal tract for efficacy. Injectable ropinirole compositions and methods that are stable for extended periods of time and that can be administered by an infusion would also be beneficial in the treatment of Parkinson's disease.